[Therapeutic effect of emodin in experimental periodonititis rats].
Through observing the change of Nitric Oxide (NO) in the peripheral blood and gingival tissue, to explore the mechanism of Emodin (EMD) in the therapy of periodontal disease. SD rats were randomly divided into four groups of thirty (group N, group P, group PL and the group PH). The periodontitis model was made and EMD was administered at PL and PH. At the 4th, 6th, 8th weeks after the animal models were established, the rats were killed respectively and the maxilla and the peripheral blood were collected. A side of maxilla was stained with HE for histological examination and the other side of gingival tissue surround ligated tooth was collected for the measurement of NO. Also, it was measured in the peripheral blood. GLM method using SPSS was used to compare changes in each of the variables over time. The levels of NO in the peripheral blood and gingival tissue in PL and PH groups were significantly lower than that in P groups(P<0.05). Emodin can take effect on periodontitis by reducing the levels of NO in the peripheral blood and gingival tissue.


Political Orientation Predicts Credulity Regarding Putative Hazards.
To benefit from information provided by other people, people must be somewhat credulous. However, credulity entails risks. The optimal level of credulity depends on the relative costs of believing misinformation and failing to attend to accurate information. When information concerns hazards, erroneous incredulity is often more costly than erroneous credulity, given that disregarding accurate warnings is more harmful than adopting unnecessary precautions. Because no equivalent asymmetry exists for information concerning benefits, people should generally be more credulous of hazard information than of benefit information. This adaptive negatively biased credulity is linked to negativity bias in general and is more prominent among people who believe the world to be more dangerous. Because both threat sensitivity and beliefs about the dangerousness of the world differ between conservatives and liberals, we predicted that conservatism would positively correlate with negatively biased credulity. Two online studies of Americans supported this prediction, potentially illuminating how politicians' alarmist claims affect different portions of the electorate.


Study of a restriction fragment length polymorphism for serum amyloid P gene in rheumatoid arthritis with amyloidosis.
Amyloidosis is a severe complication of rheumatoid arthritis (RA). A restriction fragment length polymorphism (RFLP) using MspI for the serum amyloid P gene was recently found to be associated with amyloidosis in juvenile arthritis. The aim of our study was to determine whether this RFLP could serve as a genetic marker for the development of secondary amyloidosis in RA. The prevalence of this marker was determined in 4 groups of patients: patients with amyloidosis secondary to RA; with amyloidosis secondary to various diseases excluding RA; with RA but without amyloidosis; adult controls without any known disease related to reactive amyloidosis. No significant differences were seen between these 4 groups with relation to this polymorphism, so that it cannot serve as a genetic marker for amyloidosis complicating RA in our population.


Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas.
Analysis of the immunoglobulin κ light chain (IGK) gene is an alternative method for B-cell clonality assessment in the diagnosis of mature B-cell proliferations in which the detection of clonal immunoglobulin heavy chain (IGH) gene rearrangements fails. The aim of the present study was to evaluate the added value of standardized BIOMED-2 assay for the detection of clonal IGK gene rearrangements in the diagnostic setting of suspected B-cell lymphomas. With this purpose, 92 specimens from 80 patients with the final diagnosis of mature B-cell lymphoma (37 specimens), mature T-cell lymphoma (26 specimens) and reactive lymphoid proliferation (29 specimens) were analyzed for B-cell clonality. B-cell clonality analysis was performed using the BIOMED-2 IGH and IGK gene clonality assays. The determined sensitivity of the IGK assay was 67.6%, while the determined sensitivity of the IGH assay was 75.7%. The sensitivity of combined IGH+IGK assay was 81.1%. The determined specificity of the IGK assay was 96.2% in the group of T-cell lymphomas and 96.6% in the group of reactive lesions. The determined specificity of the IGH assay was 84.6% in the group of lymphomas and 86.2% in the group of reactive lesions. The comparison of GeneScan (GS) and heteroduplex pretreatment-polyacrylamide gel electrophoresis (HD-PAGE) methods for the analysis of IGK gene rearrangements showed a higher efficacy of GS analysis in a series of 27 B-cell lymphomas analyzed by both methods. In the present study, we demonstrated that by applying the combined IGH+IGK clonality assay the overall detection rate of B-cell clonality was increased by 5.4%. Thus, we confirmed the added value of the standardized BIOMED-2 IGK assay for assessment of B-cell clonality in suspected B-cell lymphomas with inconclusive clinical and cyto/histological diagnosis.


Synthesis and herbicidal activity of N,N-diethyl-3-(arylselenonyl)-1H-1,2,4-triazole-1-carboxamide.
Based on the carbamoyl triazole herbicide Cafenstrole, 12 novel selenium-containing compounds were designed and synthesized. All of the compounds were characterized and confirmed by IR, 1H NMR, and high-resolution mass spectroscopy. The bioassay tests showed that some of the compounds (C2, C4, C(7-8), and C12) exhibited good inhibitory activity against cucumber (Cucumis sativus L.) and semen euphorbiae (Leptochloa chinensis N.). Especially, compound C6 inhibited the growth of cucumber and semen euphorbiae by >90% at a concentration of 1.875 microg/mL, and the inhibition of the compound on the rice (Oryza sativa L.) was only 8.3% at a concentration of 7.5 microg/mL, which indicated a higher selectivity between weed and rice than that shown by Cafenstrole.


[Emerging concept of the production and absorption of cerebrospinal fluid, and recent progress in the diagnosis and treatment of iNPH].
Recently, there has been emerging a new attractive hypothesis that cerebrospinal fluid (CSF) is not circulating or absorbed from arachnoid villi, but absorbed from capillaries of the brain surface to vasculature or excreting through arterial walls and cribriform plate to cervical lymph nodes. About 90% of patients with iNPH (idiopathic normal pressure hydrocephalus) show DESH (Disproportionately Enlarged Subarachnoid-space Hydrocephalus) sign on brain CT/MRI. Identification of the DESH sign is important for the diagnosis of iNPH, and it is helpful for the judgement whether DESH sign is positive or not to detect apparent hyperperfusion in the high-convexity of the brain in iNPH patients with N-isopropyl-p-[(123)I] iodoamphetamine (IMP) single photon emission computed tomography (SPECT). We have named this characteristic finding in IMP-SPECT as the CAPPAH (Convexity APPArent Hyperperfusion) sign, and would like to emphasize its usefulness in the clinical diagnosis of iNPH.


A Novel Subfamily of Endo-β-1,4-Glucanases in Glycoside Hydrolase Family 10.
As classified by the Carbohydrate-Active Enzymes (CAZy) database, enzymes in glycoside hydrolase (GH) family 10 (GH10) are all monospecific or bifunctional xylanases (except a tomatinase), and no endo-β-1,4-glucanase has been reported in the family. Here, we identified Arcticibacterium luteifluviistationis carboxymethyl cellulase (AlCMCase) as a GH10 endo-β-1,4-glucanase. AlCMCase originated from an Arctic marine bacterium, Arcticibacterium luteifluviistationis SM1504T It shows low identity (<35%) with other GH10 xylanases. The gene encoding AlCMCase was overexpressed in Escherichia coli Biochemical characterization showed that recombinant AlCMCase is a cold-adapted and salt-tolerant enzyme. AlCMCase hydrolyzes cello- and xylo-configured substrates via an endoaction mode. However, in comparison to its significant cellulase activity, the xylanase activity of AlCMCase is negligible. Correspondingly, AlCMCase has remarkable binding capacity for cello-oligosaccharides but no obvious binding capacity for xylo-oligosaccharides. AlCMCase and its homologs are grouped into a branch separate from other GH10 xylanases in a phylogenetic tree, and two homologs also displayed the same substrate specificity as AlCMCase. These results suggest that AlCMCase and its homologs form a novel subfamily of GH10 enzymes that have robust endo-β-1,4-glucanase activity. In addition, given the cold-adapted and salt-tolerant characters of AlCMCase, it may be a candidate biocatalyst under certain industrial conditions, such as low temperature or high salinity.IMPORTANCE Cellulase and xylanase have been widely used in the textile, pulp and paper, animal feed, and food-processing industries. Exploring novel cellulases and xylanases for biocatalysts continues to be a hot issue. Enzymes derived from the polar seas might have novel hydrolysis patterns, substrate specificities, or extremophilic properties that have great potential for both fundamental research and industrial applications. Here, we identified a novel cold-adapted and salt-tolerant endo-β-1,4-glucanase, AlCMCase, from an Arctic marine bacterium. It may be useful in certain industrial processes, such as under low temperature or high salinity. Moreover, AlCMCase is a bifunctional representative of glycoside hydrolase (GH) family 10 that preferentially hydrolyzes β-1,4-glucans. With its homologs, it represents a new subfamily in this family. Thus, this study sheds new light on the substrate specificity of GH10.


Thermophilisation of communities differs between land plant lineages, land use types and elevation.
Bryophytes provide key ecosystem services at the global scale such as carbon storage and primary production in resource limited habitats, but compared to vascular plants knowledge on how these organisms face recent climate warming is fragmentary. This is particularly critical because bryophytes differ fundamentally from vascular plants in their ecophysiological and biological characteristics, so that community alterations most likely have different dynamics. In a comparative approach, we analysed thermophilisation of bryophyte and vascular plant communities in 1146 permanent plots distributed along an elevational gradient of nearly 3.000 m in Switzerland (Central Europe) that were visited in 5-years intervals between 2001 and 2021. We estimated thermophilisation from changes in unweighted mean temperature indicator values of species, compared it to expected thermophilisation rates given the shift of isotherms and addressed differences between the two lineages, major land use types (managed grasslands, forests, unmanaged open areas), life strategy types (long- and short-lived species) and in elevation. Thermophilisation of bryophyte communities was on average 2.1 times higher than of vascular plant communities and at high elevations it approximated the expected rate given the shift of isotherms. Thermophilisation of both, bryophyte and vascular plant communities was not driven by a loss of cryophilic species but by an increase in thermophilic and mesophilic species, indicating an in-filling process. Furthermore, our data show that thermophilisation is higher in managed grasslands than in forests. We suggest that the higher responsiveness of bryophytes compared to vascular plants depends on their poikilohydry and dispersal capacity and that lower thermophilisation of forests communities is related to the buffering effect of microclimatic conditions in the interior of forests. Our study emphasises the heterogeneity of climate warming effects on plants because response dynamics differ between taxonomic groups as well as between land use types and along elevational gradients.


Therapeutic efficacy of intra-cochlear administration of methylprednisolone after acoustic trauma caused by gunshot noise in guinea pigs.
The therapeutic efficacy of cochlear infusion of methylprednisolone (MP) after an impulse noise trauma (170dB SPL peak) was evaluated in guinea pigs. The compound action potential threshold shifts were measured over a 14 days recovery period after the gunshot exposure. For each animal, one of the cochlea was perfused directly into the scala tympani with MP during 7 days via a mini-osmotic pump, whereas the other cochlea was not pump-implanted. The functional study of hearing was supplemented by histological analysis. Forty eight hours after the trauma, significant differences between auditory threshold shifts in the implanted and non-implanted ears were observed for frequencies above 8kHz. At day 7, the difference was significant for only one frequency and no difference was observed after 14 days recovery. Cochleograms showed that the hair cell losses were significantly lower in the MP treated ears. This work indicates that direct infusion of MP into perilymphatic space accelerates hearing recovery, reduces hair cell losses after impulse noise trauma but does not limit permanent threshold shifts.


The immediate postimplantation development of tetraploid mouse blastocysts.
The development during and immediately after the implantation period of 143 tetraploid blastocysts was studied both in vitro and in vivo; 58-7% in vitro and 38-8% in vivo were found to exhibit the changes associated with the early implanting blastocyst, i.e. giant cell transformation of the trophoblast and induction of the decidual cell reaction in the uterus. Of these 38-7% in vitro and 19-4% in vivo showed evidence of inner cell mass function during this time but only two in each system could be claimed as showing normal development. Examination of the developing blastocyst leads to the conclusion that lack of cell numbers in the inner cell mass is the most likely reason for the poor development of tetraploid embryos and suggests that the minimum number of ICM cells required to fulfil its role in embryogenesis is between four and eight.


Finite size scaling and first-order phase transition in a modified XY model.
Monte Carlo simulation has been performed in a two-dimensional modified XY -model first proposed by Domany [Phys. Rev. Lett. 52, 1535 (1984)] The cluster algorithm of Wolff has been used and multiple histogram reweighting is performed. The first-order scaling behavior of the quantities such as specific heat and free-energy barrier are found to be obeyed accurately. While the lowest-order correlation function was found to decay to zero at long distance just above the transition, the next-higher-order correlation function shows a nonzero plateau.


Specific orofacial problems experienced by musicians.
Patients who play musical instruments (especially wind and stringed instruments) and vocalists are prone to particular types of orofacial problems. Some problems are caused by playing and some are the result of dental treatment. This paper proposes to give an insight into these problems and practical guidance to general practice dentists. Information in this paper is gathered from studies published in dental, music and occupational health journals, and from discussions with career musicians and music teachers. Orthodontic problems, soft tissue trauma, focal dystonia, denture retention, herpes labialis, dry mouth and temporomandibular joint (TMJ) disorders were identified as orofacial problems of career musicians. Options available for prevention and palliative treatment as well as instrument selection are suggested to overcome these problems. Career musicians express reluctance to attend dentists who are not sensitive to their specific needs. General practitioner dentists who understand how the instruments impact on the orofacial structures and are aware of potential problems faced by musicians are able to offer preventive advice and supportive treatment to these patients, especially those in the early stages of their career.


Effect of phenobarbitone on pituitary gland of male albino mice.
The effects of phenobarbitone on gonadotrophs and lactotrophs of pituitary gland were studied in male albino mice which were administered phenobarbitone 50 mg/kg body weight intraperitoneally (ip) daily for 14 days. A group of control mice were administered saline ip. In the experimental group, there was significant reduction in the average cell population of FSH cells in the cephalomedian area (P < 0.001) and in the lateral lobe (P < 0.01). The average volume of both FSH and LH cells was also significantly reduced (P < 0.001). The changes in the gonadotrophs of the experimental group could be attributed to the negative feedback action of testosterone which is being secreted from hypertrophied Leydig cells of testis.


Involvement of the 5'-untranslated region in cold-regulated expression of the rbpA1 gene in the cyanobacterium Anabaena variabilis M3.
Transcript of the rbpA1 gene in Anabaena variabilis accumulates significantly at low growth temperatures below 28 degreesC. This accumulation was maximal at 16 degreesC. Accumulation of the rbpA1 transcript was completely abolished by rifampicin, but not by chloramphenicol. Photosynthesis was not required for this cold-induced accumulation. This accumulation of transcript was partly accounted for by increased stability of the rbpA1 transcript at low temperature. Expression of chimeric genes containing 3'-deleted rbpA1 sequences fused to the lacZ gene was regulated by low temperature when almost the entire 5'-untranslated region (5'-UTR) remained undeleted. Further deletion resulted in constitutive expression of the chimeric gene. The 5'-UTR sequence formed two types of complexes in vitro with protein extract from cells grown at 38 degreesC, but not with extract from the 22 degreesC grown cells. Affinity purification identified polypeptides of 75 and 32 kDa in Complex 1 and a 72 kDa polypeptide in Complex 2. These results are compatible with a model in which expression of the rbpA1 gene is regulated by transcriptional derepression at low temperature, although additional mechanisms, such as regulation of mRNA stability, might also contribute to temperature-dependent regulation.


Conversion of Thermobifida fusca free exoglucanases into cellulosomal components: comparative impact on cellulose-degrading activity.
Cellulosomes are multi-enzyme complexes produced by certain anaerobic bacteria that exhibit efficient degradation of plant cell wall polysaccharides. To understand their enhanced levels of hydrolysis, we are investigating the effects of converting a free-cellulase system into a cellulosomal one. To achieve this end, we are replacing the cellulose-binding module of the native cellulases, produced by the aerobic bacterium Thermobifida fusca, with a cellulosome-derived dockerin module of established specificity, to allow their incorporation into defined "designer cellulosomes". In this communication, we have attached divergent dockerins to the two exoglucanases produced by T. fusca exoglucanase, Cel6B and Cel48A. The resultant fusion proteins were shown to bind efficiently and specifically to their matching cohesins, and their activities on several different cellulose substrates were compared. The lack of a cellulose-binding module in Cel6B had a deleterious effect on its activity on crystalline substrates. In contrast, the dockerin-bearing family-48 exoglucanase showed increased levels of hydrolytic activity on carboxymethyl cellulose and on both crystalline substrates tested, compared to the wild-type enzyme. The marked difference in the response of the two exoglucanases to incorporation into a cellulosome, suggests that the family-48 cellulase is more appropriate than the family-6 enzyme as a designer cellulosome component.


Severe Hypokalemia Masquerading Myocardial Ischemia.
An advanced degree of body potassium deficit may produce striking changes in the electrocardiogram (ECG). These changes can result in incidental findings on the 12-lead ECG or precipitate potentially life-threatening dysrhythmias. Although usually readily recognized, at times these abnormalities may be confused with myocardial ischemia. The object was to report a case of severe hypokalemia mimicking myocardial ischemia. A 33-year-old, previously healthy man, presented to the Emergency Department (ED) with a progressive weakness and chest discomfort. The electrocardiogram showed a marked ST-segment depression in leads II, III, aVF, V1-V6. The initial diagnosis was non ST-elevation myocardial infarction. Echocardiography was normal and troponin levels were within normal limits. A more detailed history revealed that the patient had an episode of acute gastroenteritis with diarrhea and vomiting. Serum chemistries were notable for a potassium concentration of 1,8 mmol per liter. With aggressive electrolyte correction, the ECG abnormalities reverted as potassium levels normalized. Hypokalemia induced ST-segment depression may simulate myocardial ischemia. The differential diagnosis might be difficult, especially in the cases when ST changes are accompanied with chest discomfort.


NO-Synthase Activity in Patients with Coronary Heart Disease Associated with Hypertension of Different Age Groups.
Coronary heart disease is the leading cause of death and disability worldwide. Hypertension is a major independent risk factor for the development of CHD. Abnormalities in NO generation or activity have been proposed as a major mechanism of CHD. The purpose of this article is to determine the activity of eNOS and iNOS in patients with isolated CHD and CHD associated with HT of different age groups. Fifty patients with isolated CHD and 42 patients with CHD associated with HT were enrolled in this study. NOS activity was determined by nitrite anion formed in the reaction. A statistically significant increase in iNOS activity is observed in elderly donors. In patients with isolated coronary heart disease cNOS activity is statistically significantly reduced with respect to the control group. The reduction of enzymatic activity of cNOS is more expressed in elderly patients than in middle-aged patients with coronary heart disease. Alterations in eNOS activity are more expressed in patients with coronary heart disease associated with hypertension than in patients with isolated coronary heart disease. Against the background of cNOS inhibition in the patients, a sharp increase in iNOS activity is observed. It has been shown that disturbance of endothelial function in patients with coronary heart disease associated with hypertension is characterized by reduced endothelial NO synthesis by cNOS and increased systemic NO synthesis due to increased iNOS activity. It has been found that the lack of endothelial NO and hyperproduction of »harmful« NO by iNOS are more expressed in elderly patients.


Histogenesis of beryllium-induced bone tumours.
In response to beryllium treatment, irregular bone formation starts mainly in the marrow cavity of long bones, preceding neoplastic growth. Irregular medullary bone formation may be connected with the endosteum, but usually it develops in the bone marrow, independently of the endosteum. Osteogenesis in the bone marrow may be preceded by fibrosis but irregular bone may be formed also without any previous histological changes in the bone marrow. The tumour develops directly from the medullary bone. The prolonged irritation causes abnormal osteogenesis, which ultimately turns into neoplastic proliferation. Thus, the beryllium-induced bone sarcoma is, from histogenesis point of view, a hyperplaseogenic tumour. Irregular bone formation is considered a preblastomatous change, because it is closely connected with the development of the tumour and precedes it in time. The multiplicity of the tumour is explained by the "neoplastic field" theory of WILLIS.


Changes in lung function and respiratory muscle strength after sternotomy vs. laparotomy in patients without ventilatory limitation.
A relevant ventilatory defect occurs after sternotomy, a very common thoracic surgical opening. The mechanism of the ventilatory impairment is unclear. Moreover, until now, the effect of sternotomy on pulmonary gas exchange has scarcely been investigated. We evaluated the time-course up to recovery and changes in spirometry, maximum static inspiratory (PI(max)) and expiratory (PE(max)) mouth pressures and pulmonary gas exchange in 6 patients after sternotomy and in 8 patients after laparotomy. All patients were free of cardiopulmonary diseases and had normal preoperative lung function. Sternotomy and laparotomy decreased forced vital capacity (FVC) by 67 and 49%, respectively. Moreover, the percent decreases in PI(max), PE(max) and PaO(2) after sternotomy vs. laparotomy were respectively 54 vs. 57%, 54 vs. 60%, and 22.6 vs. 7.5% (p < 0.05). Following sternotomy, the percent decreases in FVC correlated with the percent decreases in PI(max) (p < 0.05) and PE(max) (p < 0.01). The return to baseline values occurred after approximately 2 weeks. The present study shows that sternotomy can induce greater respiratory effects than laparotomy and suggests a relevant involvement of respiratory muscle weakness after surgical opening of the thorax. The study also supports the view that the evaluation of patient's lung function before sternotomy can be clinically relevant.


Authenticating Health Activity Data Using Distributed Ledger Technologies.
The on-demand digital healthcare ecosystem is on the near horizon. It has the potential to extract a wealth of information from "big data" collected at the population level, to enhance preventive and precision medicine at the patient level. This may improve efficiency and quality while decreasing cost of healthcare delivered by professionals. However, there are still security and privacy issues that need to be addressed before algorithms, data, and models can be mobilized safely at scale. In this paper we discuss how distributed ledger technologies can play a key role in advancing electronic health, by ensuring authenticity and integrity of data generated by wearable and embedded devices. We demonstrate how the Masked Authenticated Messaging extension module of the IOTA protocol can be used to securely share, store, and retrieve encrypted activity data using a tamper-proof distributed ledger.


Local induction of inflammation affects bone formation.
To explore the influence of inflammatory processes on bone formation, we applied a new in vivo screening model. Confined biological pockets were first created in rabbits as a response to implanted bone cement discs. These biomembrane pockets were subsequently used to study the effects of inflammatory stimuli on ectopic bone formation within biphasic calcium phosphate (BCP) constructs loaded with TNF-α, lipopolysaccharide (LPS) or lipoteichoic acid (LTA), all with or without bone morphogenetic protein (BMP)-2. Analysis of bone formation after 12 weeks demonstrated that the inflammatory mediators were not bone-inductive in combination with the BCP alone, but inhibited or enhanced BMP-induced bone formation. LPS was associated with a strong inhibition of bone formation by BMP-2, while LTA and TNF-α showed a positive interaction with BMP-2. Since the biomembrane pockets did not interfere with bone formation and prevented the leakage of pro-inflammatory compounds to the surrounding tissue, the biomembrane model can be used for in vivo approaches to study local inflammation in conjunction with new bone formation. Using this model, it was shown that the modulation of the inflammatory response could be beneficial or detrimental to the subsequent bone formation process. The co-delivery of inflammatory factors and bone-related growth factors should be further explored as a strategy to enhance the bone-forming efficacy of bone substitutes.


Is laparoscopic subtotal colectomy better than open subtotal colectomy in children?
The role of laparoscopic colectomy is not defined clearly. The aim of this study was to compare clinical outcomes of laparoscopic versus open subtotal colectomy in children with inflammatory bowel disease. Eight consecutive patients undergoing laparoscopic subtotal colectomy were compared with 10 consecutive patients undergoing open subtotal colectomy. All patients were refractory to medical management on immunosuppressive regimens. Operating time, length of postoperative stay and intravenous narcotic use, time to return of intestinal function, and perioperative complications were compared between the groups. Operating times were significantly longer in the laparoscopic group (mean laparoscopic, 4 hours 40 minutes v mean open 2 hours 25 minutes; P <.01). There was no difference between the 2 groups in length of postoperative intravenous narcotics or hospital stay. Ileostomy output occurred earlier (mean laparoscopic, 2.5 days v mean open 3.8 days; P =.01), and there was a trend toward earlier oral intake in the laparoscopic group. A total of 6 complications occurred in 4 patients in the laparoscopic group compared with 5 complications in 5 patients in the open group. Perioperative clinical outcomes, including complication rates, are similar with laparoscopic and open subtotal colectomy. Laparoscopic subtotal colectomy can be performed safely in children with improved cosmesis.


Diurnal variation in the somatic cell count of ewe milk.
The hourly variation of SCC in milk throughout the period between milkings was studied in 60 half udders of 30 Manchega ewes (10 each in first, second, and third parities) for 2 consecutive d. The interval between milkings was 12 h. The effects half udder, sampling time and day, interaction hour by day, and parity were statistically significant and explained 58.9, 11.9, 1.3, .6, and .3%, respectively, of total variance. The hourly repeatabilities of SCC and log SCC within each day (.83 and .86, respectively) were high. The SCC increased 70% in the 1st h postmilking and then gradually decreased until the next milking. The variations in SCC from 6 h postmilking were statistically significant but of less quantitative importance than those from the previous hours. The mean SCC of a.m. and p.m. milkings were very similar on both days (112 and 114 x 10(3) cells/ml). The mean SCC difference of milk between a.m. and p.m. milkings was 14%. This variation could be considered to be normal in the ewe for an interval of 12 h between milkings. These results suggest the standardization of time of sampling to avoid erroneous classifications of sheep based on SCC of milk.


Airevac nurses in war zones.
Since early 1993, the flight nurses and flight medical assistants of the Canadian Air Force (CAF) have been evacuating casualties from the war zones of Bosnia, Somalia and Rwanda. It's the first time since the Korean War that Canadian medical crews have done airevacs from a theatre of war, and the evacuations have been demanding--and eye-opening--experiences.


Revascularization by percutaneous coronary intervention in a case of left main coronary artery atresia.
Left main coronary artery atresia (LMCAA) is a rare congenital anomaly of the coronary artery that may have an unfavorable prognosis if left untreated. Surgical revascularization by either coronary artery bypass grafting or coronary reconstruction osteoplasty is unanimously recognized as the treatment of choice for this condition. Here, we first report a case of LMCAA treated with revascularization by percutaneous coronary intervention (PCI) through a retrograde approach. Intravascular ultrasound revealed an unusual coronary structure for the left main artery. PCI appears to be a feasible and effective alternative to surgery for the treatment of LMCAA, particularly if a minimally invasive method is desired.


Correlation between HER2 gene amplification and protein overexpression through fluorescence in situ hybridization and immunohistochemistry in breast carcinoma patients.
In India, the incidence of breast cancer has increased in the urban population, with 1 in every 22 women diagnosed with breast cancer. It is important to know the HER2/neu gene status for a better prognostication of these patients. The aim of this study was to compare the efficacy of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) for determining HER2/neu alteration in breast carcinoma. A total of 188 histologically proven breast carcinoma cases between the years 2007 and 2011 were retrospectively analyzed on the paraffin tissue sections by both IHC and FISH techniques. FISH for HER2/neu gene amplification was performed on cases where the IHC status was already known and the results were compared. A total of 64 (30%) patients were found to be amplified and the remaining 124 (65.9%) cases were found to be unamplified through FISH. Patients observed with 3+ reading on IHC were later confirmed as unamplified in 29.5% cases through FISH. It has been confirmed with the present study that IHC is a prudent first-step technique to screen tissue samples for HER2/neu gene status, but should be supplemented with the FISH technique especially in equivocal cases.


A double dissociation of dorsal and ventral hippocampal function on a learning and memory task mediated by the dorso-lateral striatum.
The objectives of this research were to further delineate the neural circuits subserving proposed memory-based behavioural subsystems in the hippocampal formation. These studies were guided by anatomical evidence showing a topographical organization of the hippocampal formation. Briefly, perpendicular to the medial/lateral entorhinal cortex division there is a second system of parallel circuits that separates the dorsal and ventral hippocampus. Recent work from this laboratory has provided evidence that the hippocampus incidentally encodes a context-specific inhibitory association during acquisition of a visual discrimination task. One question that emerges from this dataset is whether the dorsal or ventral hippocampus makes a unique contribution to this newly described function. Rats with neurotoxic lesions of the dorsal or ventral hippocampus were assessed on the acquisition of the visual discrimination task. Following asymptotic performance they were given reversal training in either the same or a different context from the original training. The results showed that the context-specific inhibition effect is mediated by a circuit that includes the ventral but not the dorsal hippocampus. Results from a control procedure showed that rats with either dorso-lateral striatum damage or dorsal hippocampal lesions were impaired on a tactile/spatial discrimination. Taken together, the results represent a double dissociation of learning and memory function between the ventral and dorsal hippocampus. The formation of an incidental inhibitory association was dependent on ventral but not dorsal hippocampal circuitry, and the opposite dependence was found for the spatial component of a tactile/spatial discrimination.


Definition, Mechanisms and Predictors of Weight Loss Failure After Bariatric Surgery.
It has been proven that surgery is more effective than non-surgical treatment in obese patients. However, this approach has several disadvantages, especially long-term weight loss. Weight loss failures can be broadly classified into two categories; insufficient weight loss (poor responder) and weight regain. However, a unified definition has not been established yet for each category, and there is no clear standard for the post-surgery time point to be used to assess weight loss failure. In addition, analyzing factors that contribute to weight loss failure will lead to strategies for reducing it. Therefore, many researchers have been interested in this subject and have published conflicting results. This review presents a definition for and describes the mechanisms and predictors of weight loss failure after bariatric surgery.


Continuous exposure to dibromoacetic acid delays pubertal development and compromises sperm quality in the rat.
Previously our work on the haloacid by-products of drinking water disinfection focused on adult exposures. Herein we evaluate the consequence of continuous exposure to dibromoacetic acid (DBA) via drinking water through reproductive development into adulthood. An initial study in which offspring were exposed from gestation day (GD) 15 through adulthood revealed significant delays in preputial separation and vaginal opening, dose-related decreases in the fertility of cauda epididymal sperm, and dose-related diminutions in the sperm membrane protein SP22. Subsequent studies consisted of groups in which exposure ceased on postnatal day 21 (PND 21) versus adulthood. For each exposure, animals were evaluated after puberty (PND 56) as well as at adulthood (PND 120). Exposure to 4, 40, or 400 ppm DBA from GD 15 through PND 21 failed to result in any significant reproductive alterations. By contrast, continuous exposure until adulthood resulted in dose-related alterations consistent with those observed in the dose-finding study. Preputial separation and vaginal opening were delayed 4 and 3 days in males and females exposed to 400 ppm (76.3 mg/kg) DBA. This was associated with increased responsiveness of both the testis and ovary to hCG ex vivo; hCG-stimulated testosterone production by testicular parenchyma on PND 56 was increased at 4 ppm (0.6 mg/kg) DBA and higher. Finally, the quality of proximal cauda epididymal sperm was compromised by continuous exposure to DBA. The sperm membrane proteome was altered in a dose-related manner with SP22, and one of its charged variants, diminished at 40 ppm (3.6 mg/kg) DBA and higher. As more sensitive endpoints are evaluated, lower effect levels can be attributed to haloacid exposure. We are now extending our evaluations to epidemiology studies designed to evaluate sperm quality in men exposed to varying levels of disinfection by-products.


Harmonizing nanomaterial exposure methodologies in ecotoxicology: the effects of two innovative nanoclays in the freshwater microalgae Raphidocelis subcapitata.
Layered double hydroxides (LDHs) are innovative nanomaterials (NMs) with a typical nanoclay structure (height <40 nm) consisting of layers of metallic cations and hydroxides stabilized by anions and water molecules. Upon specific triggers, anions can exchange by others in the surrounding environment. Due to this stimuli-responsive behavior, LDHs are used as carriers of active ingredients in the industrial or pharmaceutical sectors. Available technical guidelines to evaluate the ecotoxicity of conventional substances do not account for the specificities of NMs, leading to inaccuracies and uncertainty. The present study aimed to assess two different exposure methodologies (serial dilutions of the stock dispersion vs. direct addition of NM powder to each concentration) on the ecotoxicological profile of different powder grain sizes of Zn-Al LDH-NO3 and Cu-Al LDH-NO3 (bulk, <25, 25-63, 63-125, 125-250, and >250 µm) in the growth of the freshwater microalgae Raphidocelis subcapitata. Results revealed that the serial dilutions methodology was preferable for Zn-Al LDH-NO3, whereas for Cu-Al LDH-NO3 both methodologies were suitable. Thus, the serial dilutions methodology was selected to assess the ecotoxicity of different grain sizes for both LDHs. All Zn-Al LDH-NO3 grain sizes yielded similar toxicity, while Cu-Al LDH-NO3 powders with smaller grain sizes caused a higher effect on microalgae growth; thus, grain size separation might be advantageous for future applications of Cu-Al LDH-NO3s. Considering the differences between exposure methodologies for the Zn-Al LDH-NO3, further research involving other NMs and species must be carried out to achieve harmonization and validation for inter-laboratory comparison.


[Search for new MDR modifier possessing taxane skeleton].
Among new taxoids, taxuspines A-H and J-T, and known taxoids containing taxol and taxol-type compounds with an N-acylphenylisoserine group at C-13 and an oxetane ring at C-4 and C-5 isolated from stems and leaves of the Japanese yew Taxus cuspidata Sieb. et Zucc., two non-taxol-type compounds remarkably reduced CaCl2-induced depolymerization of microtubules. Furthermore, seven non-taxol-type compounds increased cellular accumulation of vincristine in multidrug-resistant(MDR) tumor cells as potent as verapamil, while taxol and taxol-type compounds did not show such an activity. In addition, the non-taxol-type compounds enhancing vincristine accumulation inhibited competitively binding of azidopine to P-glycoprotein. These results suggest that some non-taxol-type taxoids may be useful for overcoming MDR in tumor cells.


Does government oversight improve access to nursing home care? Longitudinal evidence from US counties.
Gains in life expectancy around the world have increasingly placed pressure on governments to ensure that the elderly receive assistance with activities of daily living. This research examines the impact of government oversight of Medicaid payment policies on access to nursing home care services in the United States. Variation in price levels induced by a federal policy shift in 1997 is used to identify the effect of Medicaid reimbursements on the number of nursing homes and beds available. Court rulings prior to the policy change are used to categorically define a range of oversight treatments at the state level. Difference-in-differences estimates indicate a significant decline in access to nursing home care services for individuals living in states in which courts consistently ruled that Medicaid reimbursements did not meet the minimum standard implied by federal law. The findings suggest that nursing home care services were made more accessible through a combination of legislative and judicial oversight of Medicaid payment policies.


Effects of hemoglobin-based oxygen carriers on blood coagulation.
For many decades, Hemoglobin-based oxygen carriers (HBOCs) have been central in the development of resuscitation agents that might provide oxygen delivery in addition to simple volume expansion. Since 80% of the world population lives in areas where fresh blood products are not available, the application of these new solutions may prove to be highly beneficial (Kim and Greenburg 2006). Many improvements have been made to earlier generation HBOCs, but various concerns still remain, including coagulopathy, nitric oxide scavenging, platelet interference and decreased calcium concentration secondary to volume expansion (Jahr et al. 2013). This review will summarize the current challenges faced in developing HBOCs that may be used clinically, in order to guide future research efforts in the field.


Thirteen kinds of Chinese medicine injections for acute exacerbation of chronic obstructive pulmonary disease: Protocol for a systematic review and network meta-analysis.
Chinese medicine injections (CMIs) are extensively applied to the therapy of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in mainland China. Up to 13 different kinds of CMIs are reportedly often used for treating chronic obstructive pulmonary disease, yet, rarely head to head comparison of tests are used to decide the relative consequent among the distinct CMIs. Network meta-analysis (NMA) will be performed to further compare the effects of 13 different CMI, including direct and indirect comparisons of different CMI. From now until April 2019, a systematic and comprehensive literature search will be conducted in both English and Chinese databases, including Medline, Embase, Cochrane library, Chongqing VIP information, Wanfang Database, China national knowledge infrastructure database, and Sino Med. Randomized controlled trials will be included related to CMI therapy for AECOPD. We will assess the quality of the included trials in accordance with the risk of bias tools in Cochrane manual 5.1.0. We will use the grading of recommendations assessment development, and evaluation method to assess the certainty of the estimated evidence from the NMA. STATA 14.0 will be used for data analysis. The purpose of this systematic evaluation and NMA was to summarize and rank the direct and indirect evidence for 8 different types of CMI. The NMA's findings will be reported in accordance with preferred reporting items for systematic reviews and meta analyses-NMA statement. Upon completion, NMA results will be submitted to a peer-reviewed journal. With NMA, this study will provide evidence for the selection of CMI for patients with AECOPD. The results will provide information to clinicians, bridge the evidence gap and identify promising CMI targets for future trials. PROSPERO CRD 42019132955.


Characterization of Leptospira santarosai Serogroup Grippotyphosa Serovar Bananal Isolated from Capybara ( Hydrochaeris hydrochaeris ) in Brazil.
Leptospirosis is a widespread zoonosis caused by bacteria of the genus Leptospira. Rodents appear to be the most important reservoirs of infection. They contaminate the environment and food and can transmit the pathogen when they are consumed by carnivores. Capybara ( Hydrochaeris hydrochaeris ) are efficient reservoirs of Leptospira, and because they are in close contact with farm animals and are found in semiurban areas, they represent a risk to public health. We isolated five Leptospira strains from capybara kidneys in Sao Paulo State, Brazil, in 2001 and typed them using serologic and molecular techniques. These strains include the Leptospira santarosai serogroup Grippotyphosa serovar Bananal. Pulsed field gel electrophoresis resulted in a unique pattern distinct from the reference strains, and the isolates clustered with greater than 85% similarity. The isolates also presented higher growth rates than other Leptospira serovars, with high minimal inhibitory concentration values for most of the tested antibiotics, with the exception of penicillin and ampicillin. This isolation and characterization of the L. santarosai serogroup Grippotyphosa serovar Bananal from capybara, highlights the importance of wild and sinantropic rodents as carriers of pathogenic leptospires.


[Pregnant women's attitudes towards the acceptable age limits for conceiving and giving birth to a child].
To assess whether there are socially determined permissible and desirable age limits for conceiving and childbirth among pregnant women in Bulgaria and their relation to age, general and obstetrical medical history, method of conception, level of education and whether pregnancy has been postponed or not. 388 patients from the Fetal Medicine Clinic of the State University Hospital "Maichin Dom" in Sofia were provided with anonymous questionnaires, containing 38 questions. Two of the questions were essensial: 1) "What is the maximal permissible age for a woman to become pregnant and give birth to a child?". 2) "What is the maximal desirable age for a woman to become pregnant and deliver the planned numberof children?". The questionnaire contained also 23 questions related to the demographic characteristics of the participants and to their general and obstetric medical history. Data were processed with SPSS 13.0 statistical package. Descriptive and comparative analysis was performed after grouping according to one or mare chracteristics. P values < 0.05 were considered statistically significant. 54.2% (208/388) of the respondents determined a limit of the maximal permissible age for woman to conceive and give birth to a child. 53.4% (111/208) of them set the age limit of 40 years (28.9% of all patients). 63.6% (245/388) of the interrogated set a desirable age limit for conception and giving birth. Among then 82.9% (203/245) have set the limit at 40 years. The factors that influenced significantly the attitude towards the permissible age forconception/giving birth were the mode of conception, age and the level of education. Patients who had conceived spontaneously and had higher educational level were more confident when assessing the permissible age for conception/giving birth. Patients who had conceived by IVF/ICSI were significantly less confident answering the questions about age limits. The understanding for the permissible age for conception was not influenced by past obstetric history, deliberate postponemend of reproductive plans and the presence of chronic medical disorders. The understanding that pregnancy is always permissible (irrespective of age) was not influenced significantly by any of the factors. The understanding about the desirable age for conceiving/giving birth was influenced significantly only by the educational level--patients with higher degree of education were more confident in setting a desirable age limit.


[The relationship between optimistic bias about health crisis and health behavior].
This study was performed to identify the relationship between optimistic bias about health crisis and health behavior of Korean adults in a crisis of health, and to prepare baseline data for developing a health education and promotion program. Study subjects were 595 adults aged from 19 to 64 who live in Korea. Data were collected through questionnaires administered by one interviewer. Descriptive statistics and Pearson's correlation coefficient were calculated using the SPSS program. The average score for optimistic bias about health crisis was 2.69, and that for health behavior was 107.05. The optimistic bias about health crisis showed a significantly positive correlation with health behavior (r=.187, p=.000). To make our results more useful, it is necessary to identity the causal relationship between health attitudes as an explanatory variable and optimistic bias as an outcome variable. In addition, a relatively low score in optimistic bias from this research compared to other studies must be explained through further studies considering unique Korean cultural background. Moreover, research of the relationship between optimistic bias about health crisis and health behavior looking at people who don't have good health behaviors is needed.


Vegetarians have a reduced skeletal muscle carnitine transport capacity.
Ninety-five percent of the body carnitine pool resides in skeletal muscle where it plays a vital role in fuel metabolism. However, vegetarians obtain negligible amounts of carnitine from their diet. We tested the hypothesis that muscle carnitine uptake is elevated in vegetarians compared with that in nonvegetarians to maintain a normal tissue carnitine content. Forty-one young (aged ≈22 y) vegetarian and nonvegetarian volunteers participated in 2 studies. The first study consisted of a 5-h intravenous infusion of l-carnitine while circulating insulin was maintained at a physiologically high concentration (≈170 mU/L; to stimulate muscle carnitine uptake) or at a fasting concentration (≈6 mU/L). The second study consisted of oral ingestion of 3 g l-carnitine. Basal plasma total carnitine (TC) concentration, 24-h urinary TC excretion, muscle TC content, and muscle carnitine transporter [organic cation transporter 2 (OCTN2)] messenger RNA and protein expressions were 16% (P < 0.01), 58% (P < 0.01), 17% (P < 0.05), 33% (P < 0.05), and 37% (P = 0.09) lower, respectively, in vegetarian volunteers. However, although nonvegetarians showed a 15% increase (P < 0.05) in muscle TC during l-carnitine infusion with hyperinsulinemia, l-carnitine infusion in the presence or absence of hyperinsulinemia had no effect on muscle TC content in vegetarians. Nevertheless, 24-h urinary TC excretion was 55% less in vegetarians after l-carnitine ingestion. Vegetarians have a lower muscle TC and reduced capacity to transport carnitine into muscle than do nonvegetarians, possibly because of reduced muscle OCTN2 content. Thus, the greater whole-body carnitine retention observed after a single dose of l-carnitine in vegetarians was not attributable to increased muscle carnitine storage.


Treatment of urticaria: a clinical and mechanistic approach.
This manuscript describes the recommended therapy of chronic spontaneous urticaria based on our understanding of the pathogenesis of hive formation. Thus, the mechanism of action of each medication is elaborated in addition to a discussion of clinical utility. The main drugs are antihistamines, omalizumab, and cyclosporine with a success rate of 40-55, 65-80, and 70-80%, respectively. Used in sequence, over 90% of patients can be successfully treated. The addition of omalizumab represents a major advance because of its efficacy, easy utility, and favorable side-effect profile. The interaction with IgE eliminates any reaction with antigens to which it might be directed, down regulates IgE receptors on mast cells and basophils, and leads to down-regulation of mast cell functions with amelioration of hives. The use of antihistamines in high dosage (at least four times a day) is effective in close to half the patients with CSU. For antihistamine resistance, the use of omalizumab has revolutionized therapy of antihistamine-resistant cases because of its efficacy and excellent side-effect profile. If the response is insufficient, cyclosporine is the next choice. Patients should be monitored regarding any adverse effects on blood pressure or renal function. All these are far safer than extended use of corticosteroid.


High-level overexpression of the Arabidopsis HsfA2 gene confers not only increased themotolerance but also salt/osmotic stress tolerance and enhanced callus growth.
Heat shock transcription factors (Hsfs) are the central regulators of the heat shock (HS) stress response in all eukaryotic organisms. HsfA2 is one of the Arabidopsis class A Hsfs, and the induction of HsfA2 expression in response to HS stress is highest among all 21 Arabidopsis Hsfs. In this study, it is reported that basal and acquired thermotolerance was significantly enhanced in high-level HsfA2-overexpressed transgenic lines (El2Omega::HsfA2) in comparison with wild-type plants. By contrast, the dominant negative mutants of HsfA2 (El2Omega::HsfA2DeltaC264) plants displayed reduced thermotolerance. These results indicate that the HsfA2 gene plays a role in the HS stress response. Microarray analysis of the El2Omega::HsfA2 plants identified putative target genes, which included HS stress-inducible genes and other stress-responsive genes. Salt and osmotic stress induced HsfA2 gene expression. In fact, the El2Omega::HsfA2 plants showed enhanced tolerance to these stresses, suggesting that HsfA2 was involved in multiple stress tolerance. El2Omega::HsfA2 plants showed accelerated callus growth from root explants compared with the wild type, unlike the El2Omega::HsfA2DeltaC264 plants whose growth was delayed. These observations suggest that HsfA2 plays, in addition to its role in stress tolerance, an important role in cell proliferation.


Serum aminoterminal propeptide of type III procollagen in systemic sclerosis. A follow-up--investigations in subclasses and during therapy.
Fifty-seven patients with systemic sclerosis were investigated for connective tissue turn-over related to type III collagen. Sera from 13 patients with diffuse cutaneous systemic sclerosis and 44 patients with limited cutaneous systemic sclerosis were analysed for aminoterminal propeptide of type III procollagen (PIIINP) by a radioimmunoassay based on human propeptide. Increased levels of PIIINP in serum correlated with skin involvement and the clinical course. All patients with diffuse cutaneous systemic sclerosis had levels above the normal range, and in limited cutaneous systemic sclerosis elevated PIIINP levels seemed to be correlated with rapid progression and with extension of lesions. Immunosuppressive drugs, cyclosporin A, and prednisone with or without cyclophosphamide, which were given to patients with rapid disease progression, significantly reduced PIIINP. This was also the case with penicillamine, but to a lesser degree. Our data support the suggestion that immunosuppressive agents are justified in rapidly progressive, life-threatening or disabling disease, when used with the necessary precautions. Serum PIIINP may be utilized as a marker of type III collagen fibrogenesis in systemic sclerosis and be of prognostic value. PIIINP may also be of use in the differential diagnosis between diffuse cutaneous systemic sclerosis and scleredema.


Rolling circle-replicating plasmids from gram-positive and gram-negative bacteria: a wall falls.
Rolling circle-replicating plasmids constitute a group of small, promiscuous multicopy replicons spread among eubacteria. Until recently, rolling circle replication seemed to be limited to small plasmids from Gram-positive hosts and to single-stranded bacteriophages from Gram-negative bacteria. However, characterization of two small plasmids from Gram-negative hosts has shown that this replication mechanism is general among eubacteria. This review focuses on a family of highly related promiscuous plasmids that replicate by the rolling circle mechanism, and that have been isolated from various Gram-positive bacteria and from the Gram-negative bacterium Helicobacter. They all share homologies at the leading-strand origins and at the initiator of replication proteins. The plasmids of this family have directly repeated sequences at their plus origin of replication, which is located 5' from the start point of the mRNA for the initiation of replication protein. Replication is controlled by an antisense RNA and by a transcriptional repressor protein. The features and regulatory circuits of replication of this plasmid family seem to be unique among rolling circle-replicating plasmids. Members of this family replicate autonomously in Gram-positive and -negative hosts.


Isolation of outer membrane proteins (OMP) from Salmonella cells using zwitterionic detergent and their separation by two-dimensional electrophoresis (2-DE).
We report that using the zwitterionic detergent Zwittergent Z 3-14 to isolate outer membrane proteins (OMPs) from Salmonella 048 is suitable for their separation by two-dimensional electrophoresis (2-DE) in a capillary tube system. Sample preparation is a very crucial step for any bacterial proteomic study. Some modifications were introduced to the 2-DE protocol suggested by O'Farrell and BioRad, which significantly impaired the resolution of proteins. 2-DE analysis of OMPs may be helpful in the interpretation of the variable susceptibility of Salmonella 048 rods to the bactericidal activity of serum.


Protein kinase C and cardiac dysfunction: a review.
Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure.


Playing AIDS: an experiment in popular theatre in Mali.
In Mali, an original experiment called the "useful theater" has succeeded in making the population aware of the problem of AIDS while entertaining them at the same time. Philippe Dauchez, a French stage director and teacher of dramatic art at the Institut National des Arts (INA) in Bamako, drew his inspiration from a popular theater tradition, the koteba, and created the "useful theater", whose aim is to make messages about health acceptable by presenting them in an amusing way. Five companies of actors, all former pupils of INA, regularly visit the most far flung villages to present plays on hygiene and especially on AIDS. The AIDS question is treated here with humor, though gradually the comedy turns to tragedy as one by one, towards the end of the play, the characters learn that they have contracted AIDS. The actors mime their convulsions and suffering and die on stage, despite the efforts of the healer and the doctor, who remain powerless. The aim is to show how the disease is transmitted and how to protect oneself by using a condom. After each performance a discussion is organized to make sure that the message has truly been understood, and condoms are distributed to the audience.


Degradation intermediates of polyhydroxy butyrate inhibits phenotypic expression of virulence factors and biofilm formation in luminescent Vibrio sp. PUGSK8.
Luminescent vibrios are ubiquitous in the marine environment and are the causative agents of vibriosis and mass mortality in many aquatic animals. In aquatic environments, treatments cannot be limited to the diseased population alone, therefore treatment of the entire aquatic system is the only possible approach. Thus, the use of antibiotics to treat part of the infected animals requires a dose based on the entire biomass, which results in the treatment of uninfected animals as well as non-target normal microbial flora. A treatment method based on anti-virulence or quorum quenching has recently been proposed as an effective treatment strategy for aquatic animals. Polyhydroxy butyrates (PHB) are bacterial storage molecules, which accumulate in cells under nutritional stress. The degradation of PHB releases short-chain β-hydroxy butyric acid, which may act as anti-infective molecule. To date, there is very limited information on the potential anti-infective and anti-virulence mechanisms involving PHB. In this study, we aim to examine the effect of PHB on inhibition of the virulence cascade of Vibrio such as biofilm formation, luminescence, motility behaviour, haemolysin and quorum sensing. A luminescent Vibrio PUGSK8, tentatively identified as Vibrio campbellii PUGSK8 was tested in vitro for production of extracellular virulence factors and then established as a potential shrimp pathogen based on in vivo challenge experiments. The ability of Vibrio PUGSK8 to form biofilms and the effect of PHB on biofilm formation was tested in a 96-well microtitre-plate assay system. The motility behaviour of Vibrio PUGSK8 was evaluated using twitching, swimming and swarming plate assays. Reporter strains such as Chromobacterium violaceum CV026 and Agrobacterium tumefaciens were used to detect quorum-sensing molecules. Gas chromatography-mass spectrometry spectral analysis was performed to elucidate the fragmentation pattern and structure of N-hexanoyl homoserine lactone. PHB depolymerase activity in Vibrio PUGSK8 was quantified as the amount of the enzyme solution to hydrolyse 1 μg of PHB per min. An in vivo challenge experiment was performed using a gnotobiotic Artemia assay. Of the 27 isolates tested, the Vibrio PUGSK8 strain was selected for target-specific assays based on the high intensity of luminescence and production of virulence factors. The virulence cascade detected in Vibrio PUGSK8 include luminescence, motility behaviour, biofilm formation, quorum sensing and haemolysin production. Thus inhibition/degradation of the virulence cascade would be an effective approach to contain Vibrio infections in aquatic animals. In this report, we demonstrate that the degradation intermediate of PHB effectively inhibits biofilm formation, luminescence, motility behaviour, haemolysin production and the N-acyl-homoserine lactone (AHL)-mediated quorum-sensing pathway in PUGSK8. Interestingly, the growth of Vibrio PUGSK8 remains unaffected in the presence of PHB, with PHB degradation being detected in the media. PHB depolymerase activity in Vibrio PUGSK8 results in the release of degradation intermediates include a short-chain β-hydroxy butyric acid, which inhibits the virulence cascade in Vibrio PUGSK8. Thus, a molecule that targets quorum sensing and the virulence cascade and which is species/strain-specific could prove to be an effective alternative to antimicrobial agents to control the pathogenesis of Vibrio, and thereby help to contain Vibrio outbreaks in aquatic systems.


The ties that bind. Proposed IRS regulations would put an organization's tax exemption at risk for the behavior of its executives and board.
Newly proposed IRS regulations have a simple message for not-for-profit hospitals: If you want to keep your tax-exempt status, don't engage in excess-benefit transactions. The proposals arrive as compliance officers are paying more attention to the issue. "I wouldn't say that tax awareness is high, but it's higher than ever before," says Lisa Murtha, right.


Robotic Surgery for Colorectal Cancer.
Master-slave manipulators (otherwise known as telemanipulators) were introduced into minimally invasive surgery in the 1990s to overcome the limitations of laparoscopic surgery. This led to the development of the first robotic surgical systems which, over the last 10 years, have rapidly gained acceptance among colorectal surgeons. Advantages of robotic surgical systems such as superior instrumentation and field of vision enable precise dissection in confined spaces such as the pelvis, which make it a particularly attractive tool for rectal surgery. The feasibility and safety of robotic rectal surgery is now well established and there is increasing evidence that it might offer superior peri- and postoperative outcomes when compared to laparoscopic rectal surgery. Robotic rectal surgery is easier to learn than laparoscopic surgery and the creation of a structured training program for robotic rectal surgery in Europe has facilitated the learning of this technique in an environment that promotes patient safety and improved patient outcomes through equipment fidelity and operator skill. It is foreseeable that in the near future robotic systems will become part of routine surgical practice in colorectal surgery.


Clinical presentation and etiologic factors of hirsutism in premenopausal Iranian women.
Hirsutism is a common clinical condition with different etiologies. Many of these patients have frank or subclinical abnormalities in the adrenal and ovarian steroidogenesis. The disease may be associated with other clinical signs of hyperandrogenism. The objective of this study was to investigate the clinical features of hirsutism and its etiologic factors in premenopausal Iranian women. In a cross-sectional study, 790 consecutive premenopausal women referred to the dermatology Clinics of Hazrat-e Rasool and Firoozgar University Hospitals and three private dermatology clinics during 2001 - 2003 with the clinical diagnosis of hirsutism were studied. All patients underwent detailed clinical assessment and transabdominal ultrasonography of the ovaries. Endocrinologic work-up was performed for 285 patients. Hirsutism was mild in 65%, moderate in 32.5%, and severe in 2.5% of the patients. Positive family history was found in 56.2%. Hormonal studies revealed some abnormalities in 35.2% of the patients. Coexisting medical conditions included acne in 70% of the patients, menstrual irregularity in 38.6%, androgenic alopecia in 21.3%, obesity in 6.5%, acanthosis nigricans in 4.9%, and diabetes in 0.6% of the patients. Etiology of hirsutism was identified as polycystic ovary syndrome (62.53%), idiopathic (35.19%), congenital adrenal hyperplasia (0.38%), prolactinoma (0.13%), and undetermined (1.77%). Polycystic ovary syndrome was diagnosed more frequently in women with menstrual irregularity than eumenorrheic patients (97.70% vs. 40.41%, P < 0.001). Hirsute patients frequently have either elevated androgen levels or clinical conditions associated with hyperandrogenemia. Eumenorrhea does not rule out endocrine abnormality and particularly polycystic ovary syndrome which is a common cause of hirsutism. We recommend performing endocrinologic work up, investigation of coexisting hyperandrogenic states, and evaluation of polycystic ovary syndrome in all patients with hirsutism.


Insulin, macronutrient intake, and physical activity: are potential indicators of insulin resistance associated with mortality from breast cancer?
High levels of insulin have been associated with increased risk of breast cancer, and poorer survival after diagnosis. Data and sera were collected from 603 breast cancer patients, including information on diet and physical activity, medical history, family history, demographic, and reproductive risk factors. These data were analyzed to test the hypothesis that excess insulin and related factors are directly related to mortality after a diagnosis of breast cancer. The cohort was recruited from breast cancer patients treated at the British Columbia Cancer Agency between July 1991 and December 1992. Questionnaire and medical record data were collected at enrollment and outcomes were ascertained by linkage to the BC Cancer Registry after 10 years of follow-up. The primary outcome of interest was breast cancer-specific mortality (n = 112). Lifestyle data were analyzed using Cox proportional hazards regression models to relate risk factors to outcomes, controlling for potential confounders, such as age and stage at diagnosis. Data for biological variables were analyzed as a nested case-control study due to limited serum volumes, with at least one survivor from the same cohort as a control for each breast cancer death, matched on stage and length of follow-up. High levels of insulin were associated with poorer survival for postmenopausal women [odds ratio, 1.9; 95% confidence interval (CI), 0.7-6.6, comparing highest to lowest tertile, P trend = 0.10], while high dietary fat intake was associated with poorer survival for premenopausal women (relative risk, 4.8; 95% CI, 1.3-18.1, comparing highest to lowest quartile). Higher dietary protein intake was associated with better survival for all women (relative risk, 0.4; 95% CI, 0.2-0.8, comparing highest to lowest quartile).


Prostaglandin E2 activates melanin-concentrating hormone neurons to drive diet-induced obesity.
Hypothalamic inflammation reduces appetite and body weight during inflammatory diseases, while promoting weight gain when induced by high-fat diet (HFD). How hypothalamic inflammation can induce opposite energy balance outcomes remains unclear. We found that prostaglandin E2 (PGE2), a key hypothalamic inflammatory mediator of sickness, also mediates diet-induced obesity (DIO) by activating appetite-promoting melanin-concentrating hormone (MCH) neurons in the hypothalamus in rats and mice. The effect of PGE2 on MCH neurons is excitatory at low concentrations while inhibitory at high concentrations, indicating that these neurons can bidirectionally respond to varying levels of inflammation. During prolonged HFD, endogenous PGE2 depolarizes MCH neurons through an EP2 receptor-mediated inhibition of the electrogenic Na+/K+-ATPase. Disrupting this mechanism by genetic deletion of EP2 receptors on MCH neurons is protective against DIO and liver steatosis in male and female mice. Thus, an inflammatory mediator can directly stimulate appetite-promoting neurons to exacerbate DIO and fatty liver.


Evaluation of three-layered doxycycline-collagen loaded nanofiber wound dressing.
Nanofiber wound dressings have great potential for both acute and chronic wound healing. The aim of this study is to develop a wound dressing by the electrospinning method and to determine its in vitro characteristics. The viscosity and the surface tension values of the polymer solutions used in the electrospinning were measured and their suitability for electrospinning was evaluated. Nanofiber wound dressing consists of three layers. The first and the second layers are sodium alginate and chitosan nanofibers, respectively. The core of the coaxial nanofibers that comprises the third layer of the wound dressing contains 1% polycaprolactone and 4.5% collagen, the shell comprises 2.5% doxycycline and 2.5% polyethylene oxide. The developed wound dressing comprises aligned nanofibers, with a contact angle of 38°, a work of bioadhesion value of 0.485mJ/cm2 on rat skin, a tensile strength of 2.76MPa, an elongation at break value of 7.65%, a specific surface area of 9.65m2/g and a porosity of 52.3%. The amount of doxycycline content was found to be 260μg/cm2 and the complete drug release was achieved in 15min. No cytotoxic effect was shown in cell culture studies with keratinocyte cell lines. As a result of the stability studies, it was found that the morphological, mechanical, bioadhesion and wettability properties and the amount of doxycycline remained stable for a period of 12 months at 4°C/ambient humidity condition. The developed three-layered wound dressing could be an alternative for wound healing applications.


Thoracic Duct Occlusion Leading to Intermittent Left Supraclavicular Swelling and Pancreatitis.
Intermittent left supraclavicular swelling is an uncommon and elusive condition that can lead to extensive diagnostic workups to determine the etiology and treatment. One potential cause is partial, intermittent, or complete thoracic duct occlusion (TDO). We report on a patient who presented with chronic, intermittent left supraclavicular swelling and abdominal pain that was relieved by thoracic duct angioplasty. Thoracic duct occlusion should be included in the differential diagnosis of left supraclavicular swelling. Lymphatic imaging can facilitate the diagnosis and allows for potential percutaneous treatment. Laryngoscope, 2023.


Sound absorption by clamped poroelastic plates.
Measurements and predictions have been made of the absorption coefficient and the surface acoustic impedance of poroelastic plates clamped in a large impedance tube and separated from the rigid termination by an air gap. The measured and predicted absorption coefficient and surface impedance spectra exhibit low frequency peaks. The peak frequencies observed in the absorption coefficient are close to those predicted and measured in the deflection spectra of the clamped poroelastic plates. The influences of the rigidity of the clamping conditions and the width of the air gap have been investigated. Both influences are found to be important. Increasing the rigidity of clamping reduces the low frequency absorption peaks compared with those measured for simply supported plates or plates in an intermediate clamping condition. Results for a closed cell foam plate and for two open cell foam plates made from recycled materials are presented. For identical clamping conditions and width of air gap, the results for the different materials differ as a consequence mainly of their different elasticity, thickness, and cell structure.


Structural binding evidence of the trypanocidal drugs berenil and pentacarinate active principles to a serine protease model.
Bovine trypsin is a model system for the serine protease class of enzymes, which is an important target for contemporary medicinal chemistry. Some structural and thermodynamic reports are available on its interaction with benzamidine-based compounds but no structural information is available so far on its binding modes to the active principles of the trypanocidal drugs Pentacarinate (pentamidine) and Berenil (diminazene). The crystallographic structures of bovine beta-trypsin in complex with the ligands were determined to a resolution of 1.57 A (diminazene) and 1.70 A (diminazene and pentamidine). The second benzamidine moieties in these inhibitors are bound to the enzyme in different hot spots and only few hydrogen bonds mediate these interactions. Thermodynamic parameters for the association of pentamidine with beta-trypsin reveal that this inhibitor has about 1.3-fold lower affinity than diminazene. Moreover its binding mode resembles other benzamidine-based compounds that assess the aryl binding pocket of the enzyme; however, with almost 2.5-fold higher affinity. This is the first structural evidence of the binding of Berenil and Pentacarinate active principles trypanocidal drugs to serine proteases.


Ethical decision making about animal experiments.
Laboratory animals, being vulnerable subjects, need the protection provided by adequate ethical review. This review falls primarily to Institutional Animal Care and Use Committees. A review committee's first duty is to identify which procedures ethically are unacceptable irrespective of any knowledge that might be derived. Examples are provided. These projects should be disapproved. Then, "on balance" judgments are assessed that weigh the animal harms against the potential benefits to humans. Several countries (but not the United States) use a classification system for ranking the degree of animal pain and distress. This type of assessment is essential for careful ethical analysis. Another way to enhance ethical discussion is to strive for a more balanced perspective of different viewpoints among members of decision making committees. Inclusion of representatives of animal welfare organizations and a greater proportion of nonanimal researchers would likely achieve this objective.


Determination of levels of lead contamination in food and feed crops.
A rapid, precise procedure is described for the determination of lead in food and feed products with electrothermal atomic absorption spectrophotometry. Samples were mineralized in a microwave acid digestion bomb in the presence of nitric acid and vanadium pentoxide. Lead concentrations were determined directly from digested samples. The detection limit was 0.04 ng/mL. Accuracy and precision were checked against National Institute of Standards and Technology standard reference material. The analytical method was tested with 51 food and feed crops from Mediterranean zones in Spain and found to be suitable for these products. Lead concentrations in samples ranged from not detectable to 2.695 micrograms/g (fresh weight).


Acute generalized exanthematic pustulosis: a case and an overview of side effects affecting the skin caused by celecoxib and other COX-2 inhibitors reported so far.
A 55-year-old woman who was treated for periarthritis humeroscapularis with celecoxib (Celebrex) developed a generalized pustular exanthema on the head and upper trunk, accompanied by fever, leukocytosis and increased erythrocyte sedimentation rate. The histological findings were subcorneal pustules, necrotic keratinocytes, edema in the upper dermis and polymorphic perivascular infiltrates. Four days after stopping celecoxib, the pustules disappeared without any treatment. Four weeks after disappearance of the skin lesions, celecoxib demonstrated a positive lymphocyte stimulation test. In this article, we present to our knowledge the first case of acute generalized exanthematic pustulosis caused by celecoxib, and we give an overview of the side effects affecting the skin caused by celecoxib and other cyclooxygenase type 2 inhibitors reported so far.


[Extracellular polysaccharides of saprotrophic mycobacteria and patterns of their formation].
Exocellular polysaccharides were synthesized by ten strains of 7 saprotrophic mycobacterial species in parallel with their growth. The cultures grew and produced polysaccharides more rapidly in a medium with glucose than in a medium with n-hexadecane. The polymers are homogeneous acid heteroglycans of the regular structure. All of them contain glucose and some of them contain hexuronic acid. Galactose, fucose, mannose, ramnose and pyruvic acid are found in some of the polysaccharides. The exoglycans of two mycobacterial species contain mannolactylic acid. Beta-glycosidic linkages prevail in most of the polysaccharides.


Seasonal variation, treatment outcome, and its associated factors among the snakebite patients in Somali region, Ethiopia.
Snakebite is a major cause of mortality and morbidity in many areas, particularly in the rural tropics, and is a major public health problem around the world. It also imposes significant economic burdens on snakebite victims due to treatment-related expenses and lost productivity. The purpose of this study was to assess seasonal variation, treatment outcomes, and its associated factors among snakebite in Denan health center in the Somali region, Ethiopia. A facility-based cross-sectional study was conducted from 10 to 30 September 2020 in Denan health center, Somali region, Ethiopia. All snakebite cases in Denan health center from 1 September 2015 to 31 August 2020 were included. Data were collected using a pre-tested structured checklist from the patient cards. Data were entered into EpiData version 3.1 and analyzed using SPSS version 22 (IBM SPSS Statistics, 2013). The prevalence was reported by proportion with 95% confidence interval (CI) and summary measures. Predictors were assessed using a multivariable logistic regression analysis model and reported using an adjusted odds ratio with 95% CI. Statistical significance was declared at p-value < 0. 05. The overall prevalence of poor outcome of venomous snakebites was 31.4% (95% CI 26.3% 35.4%). Study participants with an age of less than 10 years old (AOR = 2.01; 95% CI 1.39, 4.05), age between 10 and 30 years old (AOR = 2.06; 95% CI 1.39, 9.30), arrival times greater than or equal to 6 hours (AOR = 2.37; 95% CI 1.39, 4.05), and timing of snakebite (AOR = 0.49; 95% CI 0.31-0.87) were factors found to be significantly associated with poor treatment outcome. According to this study, about one in every three snakebite patients have a poor outcome. Patients with poor outcomes were those who did not improve as a result of treatment or died as a result of it. Designing appropriate engagement of public health education about snakebite prevention techniques, particularly during entry and exit of rainy seasons and establishment of appropriate case management protocol is strongly recommended, as well as increasing the accessibility or availability of antivenoms will undoubtedly have a significant impact on the reduction of mortality and disability related to that of the snakebites.


Prospective study of accidental carbon monoxide poisoning in 38 Swiss soldiers.
Carbon monoxide (CO) poisoning is associated with a wide range of non-specific symptoms, whose time course and prognostic significance are ill defined. We observed a large CO poisoning in a homogenous cohort of 38 male recruits and compared their symptoms with those of 46 unexposed controls from the same military unit. Incident and prevalent symptoms were assessed by sequential questionnaires. Carboxyhaemoglobin (COHb) concentration extrapolated to the time of rescue was 30.4 +/- 6.1%. Six recruits were initially unconscious, and five others were unable to get out of their sleeping bags without help. Dizziness was the most common symptom within the first two weeks and was reported in 92% of cases and 13% of controls, followed by headache (87% and 39%) and weakness (76% and 26%). Most symptoms were already present in the first hour, but vomiting, chest pain, and hearing disorders typically had a delayed onset. Headaches, cognitive impairment, and impaired vision were the slowest to resolve. After an initial maximum of 5.6 +/- 2.9 symptoms (p <0.0001 for the comparison with controls), cases reported 5.2 +/- 2.5 symptoms at two days, 1.9 +/- 2.3 symptoms at two weeks, and 1.3 +/-1.6 symptoms at one year (p <0.0001 for decrease over time). Initial palpitations (p = 0.002) and visual changes (p = 0.0003) were independent predictors of a higher symptom score at one year. In acute CO poisoning there are immediate and delayed symptoms suggesting different pathogenic mechanisms. Visual changes and palpitations are independent predictors of residual symptoms at one year.


Usefulness of collagen IV immunostaining for diagnosis of canine epidermolysis bullosa acquisita.
In dogs, autoimmune subepidermal blistering diseases (AISBDs) encompass several distinct entities that exhibit varying clinical signs, microscopic characteristics, prognosis, and response to treatment. The identification of targeted autoantigens is usually required to make the diagnosis, but immunological tests to determine these antigens are not commercially available. Epidermolysis bullosa acquisita (EBA) is an AISBD characterized by the production of autoantibodies against collagen VII in sublamina densa anchoring fibrils. This article reports on the usefulness of collagen IV immunostaining on paraffin-embedded skin biopsies as an aid to diagnose EBA in dogs. In this disease, collagen IV, which forms the fibrous 2-dimensional network of lamina densa, is detected more commonly above subepidermal vesicles than below. In other canine AISBDs, this is rarely the case. Collagen IV immunostaining therefore offers an inexpensive means to help making a suggestive diagnosis of EBA in the absence of serological determination of the targeted autoantigen.


Prolactin secretion in benign prostatic hypertrophy.
Prolactin secretion was evaluated in 22 patients with benign prostatic hypertrophy, before and after thyrotropin-releasing hormone stimulation. Increased prolactin reserve was found. In 11 patients, in whom the test was performed twice, the prolactin response after surgery was higher than in the pre-surgical test. The possible role of prolactin in the genesis of benign prostatic hypertrophy is discussed.


Two-Dimensional Titanium Carbide/RGO Composite for High-Performance Supercapacitors.
Ti3C2Tx, a 2D titanium carbide in the MXenes family, is obtained from Ti3AlC2 through selective etching of the Al layer. Due to its good conductivity and high volumetric capacitance, Ti3C2Tx is regarded as a promising candidate for supercapacitors. In this paper, the fabrication of Ti3C2Tx/RGO composites with different proportions of Ti3C2Tx and RGO is reported, in which RGO acts as a conductive "bridge" to connect different Ti3C2Tx blocks and a matrix to alleviate the volume change during charge/discharge process. In addition, RGO nanosheets can serve as a second nanoscale current collector and support as well for the electrode. The electrochemical performance of the as-fabricated Ti3C2Tx/RGO electrodes, characterized by CV, GCD, and EIS, are also reported. A highest specific capacitance (Cs) of 154.3 F/g at 2 A/g is obtained at the Ti3C2Tx: RGO weight ratio of 7:1 combined with an outstanding capacity retention (124.7 F/g) after 6000 cycles at 4 A/g.


Efficacy of Exercise on Breast Cancer Outcomes: A Systematic Review and Meta-analysis of Preclinical Data.
The use of preclinical models to investigate antitumor effects of exercise on breast tumor (BT) development and progression are critical. However, published results have not been quantitatively summarized or examined for potential exercise-moderating variables. We conducted this review to summarize and quantify the effect-size of exercise on BT outcomes in preclinical studies. A literature search was performed in MEDLINE, PubMed, Web of Science and System for Information on Grey Literature in Europe (SIGLE) databases. Risk of bias was assessed using SYRCLE's RoB tool. A total of 116 correlations were performed to analyze 28 preclinical studies published through December 2016, which included 2,085 animals and 51 exercise programs. Positive effects of small, medium and large magnitude were observed in tumor incidence, growth and multiplicity, respectively. In the tumor microenvironment, positive effects of large magnitude were also observed in proliferation and apoptosis but not in angiogenesis. Moderator variables correlated with higher intervention effects were identified along with a considerable heterogeneity in exercise protocols that precluded us from clearly perceiving the benefits of exercise exposure. In conclusion, exercise performed under specific conditions benefits BT outcomes. Preclinical studies with exercise designs mimicking exercise exposure that can be used in clinical contexts are needed.


Acute exacerbation in patients with liver cirrhosis: a clinicopathological study.
The incidence, clinicopathologic features and etiology of acute exacerbation occurring in patients with liver cirrhosis were assessed prospectively among 332 hepatitis B surface antigen (HBsAg) positive and 71 HBsAg negative patients. During an 11-year period and a mean follow-up duration of 26.8 months, 148 acute exacerbation occurred in 107 HBsAg positive patients and 32 episodes occurred in 18 HBsAg negative patients. The calculated annual incidence was 11.5%. The clinical, laboratory and histologic features were similar to those in patients with chronic hepatitis. Confluent hepatic necrosis and alphafetoprotein elevation over 100 ng/ml occurred frequently, particularly in HBeAg positive patients. In general, acute exacerbations in HBsAg negative patients were less severe than their HBsAg positive counterparts. Of the exacerbations in HBsAg positive patients, 54.8% of the HBeAg positive ones and 38.6% of the HBeAg negative ones were attributable to hepatitis B virus reactivation, while 4.8% and 7.9%, respectively, were due to hepatitis delta virus superinfection. The others might be the results of hepatitis non-A, non-B virus superinfection or increased piecemeal necrosis. The immediate outcome of acute exacerbations in cirrhotic patients was usually good, although 13.8% developed hepatic decompensation and 4.4% died. Further follow-up study is required to evaluate the long-term effect of the frequent occurrence of bridging hepatic necrosis, high elevation of alphafetoprotein and hepatic decompensation during acute exacerbation in cirrhotic patients.


Tetrapyrroles as Endogenous TSPO Ligands in Eukaryotes and Prokaryotes: Comparisons with Synthetic Ligands.
The 18 kDa translocator protein (TSPO) is highly 0conserved in eukaryotes and prokaryotes. Since its discovery in 1977, numerous studies established the TSPO's importance for life essential functions. For these studies, synthetic TSPO ligands typically are applied. Tetrapyrroles present endogenous ligands for the TSPO. Tetrapyrroles are also evolutionarily conserved and regulate multiple functions. TSPO and tetrapyrroles regulate each other. In animals TSPO-tetrapyrrole interactions range from effects on embryonic development to metabolism, programmed cell death, response to stress, injury and disease, and even to life span extension. In animals TSPOs are primarily located in mitochondria. In plants TSPOs are also present in plastids, the nuclear fraction, the endoplasmic reticulum, and Golgi stacks. This may contribute to translocation of tetrapyrrole intermediates across organelles' membranes. As in animals, plant TSPO binds heme and protoporphyrin IX. TSPO-tetrapyrrole interactions in plants appear to relate to development as well as stress conditions, including salt tolerance, abscisic acid-induced stress, reactive oxygen species homeostasis, and finally cell death regulation. In bacteria, TSPO is important for switching from aerobic to anaerobic metabolism, including the regulation of photosynthesis. As in mitochondria, in bacteria TSPO is located in the outer membrane. TSPO-tetrapyrrole interactions may be part of the establishment of the bacterial-eukaryote relationships, i.e., mitochondrial-eukaryote and plastid-plant endosymbiotic relationships.


Trueperella pyogenes isolated from a brain abscess of an adult roebuck (Capreolus capreolus).
The present study was designed to characterize phenotypically and genotypically a Trueperella pyogenes strain isolated from a brain abscess of an adult roebuck (Capreolus capreolus). The species identity could be confirmed by phenotypical investigations, by MALDI-TOF MS analysis, and by sequencing the 16S ribosomal RNA (rRNA) gene, the 16S-23S rRNA intergenic spacer region (ISR); by sequencing the target genes rpoB, gap, and tuf; and by detection of T. pyogenes chaperonin-encoding gene cpn60 with a previously developed loop-mediated isothermal amplification (LAMP) assay. The T. pyogenes strain could additionally be characterized by PCR-mediated amplification of several known and putative virulence factor-encoding genes which revealed the presence of the genes plo encoding pyolysin and nanH and nanP encoding neuraminidases; the genes fimA, fimC, and fimE encoding the fimbrial subunits FimA, FimC, and FimE; and the gene cbpA encoding collagen-binding protein CbpA. The present data give a detailed characterization of a T. pyogenes strain isolated from a brain abscess of a roebuck. However, the route of infection of the roebuck remains unclear.


The power of kindness: curative treatment with metronomic combination in advanced hepatocellular carcinoma.
The administration of approved systemic treatments for advanced hepatocellular carcinoma (HCC) is limited to patients with preserved liver function (Child-Pugh A/B7) and performance status. Conversely, metronomic chemotherapy can be safely administered to patients with poor clinical conditions and severe liver impairment. The metronomic schedule demonstrated to exert different anticancer mechanisms compared to that of the same agent administered at its standard schedule, including immune stimulation and the inhibition of angiogenesis and vasculogenesis. Nevertheless, metronomic chemotherapy is a nearly neglected option for the treatment of advanced HCC patients, even among those who cannot afford standard treatments. Herein, we report the case of a 40-year-old patient affected by HBV-HDV-related cirrhosis who was diagnosed with advanced HCC. The severe liver impairment (Child-Pugh B9) did not allow to administer first-line treatment with tyrosine kinase inhibitors so that the patient received metronomic capecitabine as upfront therapy. Due to the suspect of progressive disease at the first radiologic assessment, metronomic cyclophosphamide was added to capecitabine aiming to enhance its efficacy. After 4 months of treatment, complete tumor response, alpha-fetoprotein (AFP) normalization and the recovery of a Child-Pugh A were achieved. The patient was then able to undergo liver transplantation, and, after 18 months from the diagnosis, he is still free of disease recurrence. This experience emphasizes the reliability of metronomic capecitabine as a well-tolerated and effective treatment when patient's conditions prevent the administration of standard first-line treatments. In fact, metronomic capecitabine demonstrated its effectiveness in advanced HCC in retrospective and prospective analyses, leading to median progression-free survival and overall survival of, respectively, 6.03 and 14.47 months in phase II single-arm trial. Moreover, in consideration of the raising interest in immune-checkpoint inhibition in HCC, we believe that the immunomodulating effects of metronomic chemotherapy, either capecitabine or cyclophosphamide, warrant future trials exploring its combination with immunotherapy.


Orchestration of the activation of protein kinase R by the RNA-binding motif.
The protein kinase R (PKR) constitutes part of the host antiviral response. PKR activation is regulated by the N-terminus of protein, which encodes tandem RNA-binding motifs (RBMs). The full capabilities of RBMs from PKR and other proteins have surpassed the narrow specificities initially determined as merely binding double-stranded RNA. Recognition of the increased affinity of the RBM for additional RNA species has established an immunological distinction by which PKR can detect exogenous RNAs, as well as identified PKR-mediated expression of specific endogenous genes. Furthermore, as RBMs also mediate interactions with other proteins, including PKR itself, this motif connects PKR to the broader RNA metabolism. Given the fundamental importance of protein-RNA interactions, not only in the innate immune response to intracellular pathogens, but also to coordinate the cellular replication machinery, there is considerable interest in the mechanisms by which proteins recognize and respond to RNA. This review appraises our understanding of how PKR activity is modulated by the RBMs.


Ulmus macrocarpa Hance Extracts Attenuated H₂O₂ and UVB-Induced Skin Photo-Aging by Activating Antioxidant Enzymes and Inhibiting MAPK Pathways.
To protect from reactive oxygen species (ROS) damages, skin cells have evolved to have antioxidant enzymes, such as copper and zinc-dependent superoxide dismutase (SOD1), mitochondrial manganese-dependent superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR), and suppressed the expression of matrix metalloproteinases (MMPs) through the mitogen-activated protein kinase (MAPK) signaling pathways, such as c-Jun N-terminal kinase (JNK) and p38. Bioactive compounds analyses were performed using a high-performance liquid chromatography-photodiode array detector (HPLC-PDA) system. The antioxidant activity of Ulmus macrocarpa Hance (UMH) extracts was estimated in vitro. The anti-aging activity of UMH extracts was estimated in vivo using the SKH-1 hairless mice. The UMH extracts reduced the H₂O₂-induced intracellular ROS production and the cell damages in human dermal fibroblasts (HDFs). Moreover, the H₂O₂-induced phosphorylation of JNK and p38 was detected in HDF and UMH extracts blocked the phosphorylation. These results suggest that UMH extracts can reduce the expression of MMPs and the reduced MMPs lead to the inhibition of collagen degradation. In addition, oral administration of the UMH extracts decreased the depth, thickness, and length of wrinkles on UVB exposed hairless mice. Therefore, UMH extracts play an advantage of the functional materials in antioxidant and anti-aging of skin.


Frequency of inhibitors of daphnid trypsin in the widely distributed cyanobacterial genus Planktothrix.
Recent findings showed that inhibition of the digestive enzyme trypsin by cyanobacterial metabolites can result in the death of the microcrustacean Daphnia. Compounds that are active against daphnid trypsin can therefore be considered as potentially toxic to Daphnia. Here we reported on the frequency of such compounds in the widely distributed cyanobacterial genus Planktothrix. Of the 89 Planktothrix strains analysed, about 70% produced inhibitors of daphnid trypsin. The strains tested positive represented three common Planktothrix species and were isolated from diverse localities and geographical regions. Our findings suggest therefore that inhibitors of daphnid trypsin are common in Planktothrix and maybe other cyanobacterial genera. These compounds should therefore be considered in future studies on the chemical ecology of cyanobacteria.